Isolation, drug sensitivity, and some biochemical and genetical properties of macromomycin-resistant mouse lymphoblastoma l5178y cells

A macromomycin (MCR)-resistant subline of mouse lymphoblastoma L5178Y cells was isolated after successive treatment of tumorbearing mice with the antibiotic for 7 transplant generations, followed by cloning in culture in MCR-containing soft agar medium. The resistant cell line was about 17 times more resistant to MCR than was the parental cell line and exhibited cross-resistance to neocarzinostatin, mitomycin C and adriamycin in a similar degree to MCR. No significant cross-resistance was observed with aclarubicin, bleomycin and neo-thramycin. Alkaline phosphodiesterase activity in the plasma membrane of resistant cells was higher than that of parental cells. Uptake and efflux studies with [3H]adriamycin suggested that the resistance is due to decreased uptake and increased efflux of the antibiotic in resistant cells. Hybridization studies with MCR-sensitive and -resistant cells showed that the MCR resistance is a codominant trait in somatic cell hybrids.